Impact of Menopause and Menopausal Hormone Therapy on Liver–Kidney–Metabolic Health

Abstract

Menopause is associated with unfavorable metabolic changes that may contribute to the development of metabolic dysfunction-associated steatotic liver disease (MASLD), chronic kidney disease (CKD), and increased cardiometabolic risk. Within the evolving cardiovascular-kidney-metabolic (CKM) framework, MASLD is increasingly recognized as a key driver rather than an outcome of metabolic dysfunction. The liver and kidneys closely interact to regulate metabolism, detoxification, ketogenesis, and endocrine signaling, which together influence whole-body metabolic homeostasis. Menopause and the menopausal transition may modify these interactions through alterations in body fat distribution, insulin sensitivity, inflammatory signaling, and hepatic and renal physiology, thereby contributing to disruption of the increasingly recognized liver-kidney-metabolic (LKM) axis. Advanced MASLD, owing to liver fibrosis, may further accelerate CKD through systemic insulin resistance, subclinical inflammation, gut dysbiosis, and accumulated nephrotoxic metabolites. Menopausal hormone therapy (MHT) may partially mitigate these alterations; however, its effects on the LKM axis are variable and context-dependent according to timing, formulation, route of administration, and baseline metabolic phenotype. Current evidence does not support the use of MHT for the prevention or treatment of MASLD or CKD, and treatment should be guided by established indications. Understanding menopause as a systems-level modifier of LKM health may therefore support more personalized preventive and therapeutic strategies targeting CKM health in peri- and postmenopausal women through a holistic and integrated approach.